Advanced search
Start date
Betweenand
Related content
(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Parkinson's disease and pain: Modulation of nociceptive circuitry in a rat model of nigrostriatal lesion

Full text
Author(s):
Domenici, Roberta A. [1] ; Campos, Aria Carolina P. [1] ; Maciel, Soraya T. [1] ; Berzuino, Miria B. [1] ; Hernandes, Marina S. [2] ; Fonoff, Erich T. [1, 3] ; Pagano, Rosana L. [1]
Total Authors: 7
Affiliation:
[1] Hosp Sirio Libanes, Lab Neurosci, Rua Prof Daher Cutait 69, BR-01308060 Sao Paulo, SP - Brazil
[2] Emory Univ, Dept Med, Atlanta, GA 30322 - USA
[3] Univ Sao Paulo, Sch Med, Dept Neurol, Div Funct Neurosurg, Sao Paulo, SP - Brazil
Total Affiliations: 3
Document type: Journal article
Source: Experimental Neurology; v. 315, p. 72-81, MAY 2019.
Web of Science Citations: 3
Abstract

Parkinson's disease (PD) is a neurodegenerative disorder that causes progressive dysfunction of dopaminergic and non-dopaminergic neurons, generating motor and nonmotor signs and symptoms. Pain is reported as the most bothersome nonmotor symptom in PD; however, pain remains overlooked and poorly understood. In this study, we evaluated the nociceptive behavior and the descending analgesia circuitry in a rat model of PD. Three independent experiments were performed to investigate: i) thermal nociceptive behavior; ii) mechanical nociceptive behavior and dopaminergic repositioning; and iii) modulation of the pain control circuitry. The rat model of PD, induced by unilateral striatal 6-hydroxydopamine (6-OHDA), did not interfere with thermal nociceptive responses; however, the mechanical nociceptive threshold was decreased bilaterally compared to that of naive or striatal saline-injected rats. This response was reversed by apomorphine or levodopa treatment. Striatal 6-OHDA induced motor impairments and reduced dopaminergic neuron immunolabeling as well as the pattern of neuronal activation (c-Fos) in the substantia nigra ipsilateral (IPL) to the lesion. In the midbrain periaqueductal gray (PAG), 6-OHDA-induced lesion increased IPL and decreased contralateral PAG GABAergic labeling compared to control. In the dorsal horn of the spinal cord, lesioned rats showed bilateral inhibition of enkephalin and p-opioid receptor labeling. Taken together, we demonstrated that the unilateral 6-OHDA-induced PD model induces bilateral mechanical hypernociception, which is reversed by dopamine restoration, changes in the PAG circuitry, and inhibition of spinal opioidergic regulation, probably due to impaired descending analgesic control. A better understanding of pain mechanisms in PD patients is critical for developing better therapeutic strategies to improve their quality of life. (AU)